The aim of this study was to determine if there are differences in cognitive flexibility in anorexia nervosa and bulimia nervosa. Fifty-three patients with an eating disorder (34 with anorexia nervosa and 19 with bulimia nervosa) and 35 healthy controls participated in the study. A battery of neuropsychological tests for cognitive flexibility was used, including Trail Making B, the Brixton Test, Verbal Fluency, the Haptic Illusion Test, a cognitive shifting task (CatBat) and a picture set test. Using exploratory factor analysis, four factors were obtained: 1: Simple Alternation; 2: Mental Flexibility; 3: Perseveration; and 4: Perceptual Shift. Patients with anorexia nervosa had abnormal scores on Factors 1 and 4. Patients with bulimia nervosa showed a different pattern, with significant impairments in Factors 2 and 4. These findings suggest that differential neuropsychological disturbance in the domain of mental flexibility/rigidity may underlie the spectrum of eating disorders. (JINS, 2004, 10, 513–520.)

Increasing evidence indicates that substance-dependent individuals (SDI) are impaired in executive control tasks relying on different systems within the prefrontal cortex (PFC). Three different functional systems have been described: the dorsolateral prefrontal cortex (DLPC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) circuits. Dysfunction within each PFC system is associated with different behavioral, cognitive, and emotional abnormalities. Few studies have conducted an exhaustive examination of all these different factors in SDI. In this study, SDI (including alcohol, cocaine, and methamphetamine polysubstance users, n = 35) were compared with healthy controls (n = 36) on a series of behavioral (Frontal Systems Behaviour Scale, FrSBe), cognitive (N-back, Go-No Go, and Wisconsin Card Sorting Tasks), and emotional (International Affective Picture System, IAPS) tasks, each of which was thought to tax a different component of these PFC functional systems. SDI showed greater behavioral problems in the apathy, disinhibition, and executive dysfunction subscales of the FrSBe. Behavioral deficits were significantly associated with several real-life domains in which SDI typically have problems. SDI also showed poorer performance on cognitive tests of working memory, response inhibition and mental flexibility, and abnormal processing of affective images from the IAPS. Cognitive, behavioral, and emotional measures were moderately correlated.This study was conducted in the Department of Neurology, University of Iowa, Iowa City, USA (JINS, 2006, 12, 405–415.)

The use of videoconference technology to deliver health care diagnostics and treatment continues to grow at a rapid pace. Telepsychiatry and telepsychology applications are well-accepted by patients and providers, and both diagnostic and treatment outcomes have generally been similar to traditional face-to-face interactions. Preliminary applications of videoconference-based neuropsychological assessment (teleneuropsychology) have yielded promising results in the feasibility and reliability of several standard tests, although large-scale studies are lacking. This investigation was conducted to determine the reliability of video teleconference (VTC) - based neuropsychological assessment using a brief battery of standard neuropsychological tests commonly used in the evaluation of known or suspected dementia. Tests included the Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised, Digit Span forward and backward, short form Boston Naming Test, Letter and Category Fluency, and Clock Drawing. Tests were administered via VTC and in-person to subjects, counterbalanced using alternate test forms and standard instructions. Two hundred two adult subjects were tested in both rural and urban settings, including 83 with cognitive impairment and 119 healthy controls. We found highly similar results across VTC and in-person conditions, with significant intraclass correlations (mean=.74; range: 0.55–0.91) between test scores. Findings remained consistent in subjects with or without cognitive impairment and in persons with MMSE scores as low as 15. VTC-based neuropsychological testing is a valid and reliable alternative to traditional face-to-face assessment using selected measures. More VTC-based studies using additional tests in different populations are needed to fully explore the utility of this new testing medium. (JINS, 2014, 20, 1–6)

The use of improvised explosive devices has become the hallmark of modern warfare and has resulted in an ever-increasing number of blast-related traumatic brain injuries (TBIs). Despite this fact, very little is actually known about the cognitive sequelae of blast-related TBIs. The purpose of the current study was to compare patterns of performance on neuropsychological measures in subjects who have sustained TBIs as a result of blast (or explosion) with those who have sustained TBIs from non-blast or blunt force trauma (motor vehicle accident, fall, assault, etc.). Participants were categorized as blast-related TBI or non-blast-related TBI and according to severity of injury (mild or moderate-to-severe). No main effects were observed in analysis of covariance between blast-related TBI participants and non-blast-related TBI participants across any of the neuropsychological variables, although an interaction was observed on a visual memory test showing stronger performance for mild blast-related and poorer performance for moderate-to-severe blast-related participants compared with both non-blast groups. Overall, the results do not provide any strong evidence that blast is categorically different from other TBI mechanisms, at least with regard to cognitive sequelae on select measures. Additional findings included a marginally increased incidence of reported posttraumatic stress disorder symptoms among blast-injured participants. (JINS, 2009, 15, 1–8.)

The dimensions of postconcussive symptoms (PCS) were examined in a prospective, longitudinal study of 186 8 to 15 year old children with mild traumatic brain injuries (TBI). Parents and children completed a 50-item questionnaire within 2 weeks of injury and again at 3 months after injury, rating the frequency of PCS on a 4-point scale. Common factor analysis with target rotation was used to rotate the ratings to four hypothesized dimensions, representing cognitive, somatic, emotional, and behavioral symptoms. The rotated factor matrix for baseline parent ratings was consistent with the target matrix. The rotated matrix for baseline child ratings was consistent with the target matrix for cognitive and somatic symptoms but not for emotional and behavioral symptoms. The rotated matrices for ratings obtained 3 months after injury were largely consistent with the target matrix derived from analyses of baseline ratings, except that parent ratings of behavioral symptoms did not cluster as before. Parent and child ratings of PCS following mild TBI yield consistent factors reflecting cognitive and somatic symptom dimensions, but dimensions of emotional and behavioral symptoms are less robust across time and raters. (JINS, 2009, 15, 19–30.)

Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker profiles did not differ from a “robust” normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline. (JINS, 2014, 20, 1–12)

Two components of verbal fluency performance—clustering (i.e., generating words within subcategories) and switching (i.e., shifting between subcategories)—were examined in patients with dementia of the Alzheimer type (DAT), patients with dementia with Parkinson's disease (DPD), nondemented patients with Parkinson's disease (NPD), and demographically matched controls. The DAT and DPD groups were impaired in the number of words generated on both phonemic and semantic fluency. The DAT group produced smaller clusters on both tasks and switched less often on semantic fluency than controls. The DPD group switched less often on both tasks and produced smaller clusters on phonemic fluency than controls. The NPD group was not impaired on any fluency variable. Thus, the total number of words generated on phonemic and semantic fluency did not discriminate the dementia groups from their respective control groups, but measures of clustering and switching did. This differential pattern of performance provides evidence for the potential usefulness of measures of switching and clustering in the assessment of dementia. (JINS, 1998, 4, 137–143.)

Cognitive evaluation in developing countries is a difficult undertaking due to low levels of schooling and particularly the illiteracy still frequent in the elderly. This study was part of the epidemiologic evaluation of dementia in Catanduva, Brazil, and had the objective of comparing the performance of illiterate and literate nondemented elderly individuals in 2 tests of long-term memory—the delayed recall of a word list from the CERAD and the delayed recall of common objects presented as simple drawings from the Brief Cognitive Screening Battery (BCSB). Fifty-one elderly subjects (23 illiterates) were evaluated, and the performance of the illiterates and literates differed in the CERAD memory test, but not in the BCSB memory test. This test may be more suitable for the assessment of long-term memory in populations with a high frequency of illiterates, and therefore might prove to be a useful screening tool for the diagnosis of dementia. (JINS, 2004, 10, 634–638.)

Demographic factors impact neuropsychological test performances and accounting for them may help to better elucidate current brain functioning. The NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neuropsychological tool, yet the original norms developed for the battery did not adequately account for important demographic/cultural factors known to impact test performances. We developed norms fully adjusting for all demographic variables within each language group (English and Spanish) separately. The current study describes the standards for individuals tested in English. Neurologically healthy adults (n=1038) and children (n=2917) who completed the NIH Toolbox norming project in English were included. We created uncorrected scores weighted to the 2010 Census demographics, and applied polynomial regression models to develop age-corrected and fully demographically adjusted (age, education, sex, race/ethnicity) scores for each NIHTB-CB test and composite (i.e., Fluid, Crystallized, and Total Composites). On uncorrected NIHTB-CB scores, age and education demonstrated significant, medium-to-large associations, while sex showed smaller, but statistically significant effects. In terms of race/ethnicity, a significant stair-step effect on uncorrected NIHTB-CB scores was observed (African American<Hispanic<White). After applying normative corrections, NIHTB-CB no longer demonstrated any significant associations with demographic factors. The previously developed norms still maintained significant associations with demographic factors, and demonstrated more variable impairment rates in segments of the healthy normative sample. Similar to other neuropsychological tests, demographic factors demonstrated significant associations with unadjusted NIHTB-CB scores. Application of fully corrected scores will help account for unwanted variance that is associated with non-clinical factors to more accurately reflect effects of disease-related changes in brain function. (JINS, 2015, 21, 378–391)

This study prospectively examined neuropsychological (NP) functioning associated with adolescent substance use and withdrawal. Participants were youths with histories of substance use disorders (n = 47) and demographically comparable youths with no such lifetime histories (n = 26). They were followed with NP testing and substance involvement interviews at 7 time points spanning 8 years, from ages 16 to 24, on average. After controlling for recent use, age, education, practice effects, and baseline NP functioning, substance use over the 8-year follow-up period significantly predicted performances on tests of memory and attention at Year 8. Additionally, withdrawal symptoms during the follow-up predicted visuospatial and attention scores at Year 8. Findings suggest that use and withdrawal may differentially impact neurocognitive functioning during youth, with heavy use leading to learning, retention, and attentional difficulties, and withdrawal leading to problems with visuospatial functioning. (JINS, 2002, 8, 873–883.)

Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals. (JINS, 2013, 19, 1–9)

The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. The neuropsychological assessment protocol for children aged 6 to 18 years is described and normative data are presented for participants in that age range (N = 385). For many measures, raw score performance improved steeply from 6 to 10 years, decelerating during adolescence. Sex differences were documented for Block Design (male advantage), CVLT, Pegboard and Coding (female advantage). Household income predicted IQ and achievement, as well as externalizing problems and social competence, but not the other cognitive or behavioral measures. Performance of this healthy sample was generally better than published norms. This linked imaging-clinical/behavioral database will be an invaluable public resource for researchers for many years to come. (JINS, 2007, 13, 729–746.)This project is supported by the National Institute of Child Health and Human Development (Contract N01-HD02-3343), the National Institute on Drug Abuse, the National Institute of Mental Health (Contract N01-MH9-0002), and the National Institute of Neurological Disorders and Stroke (Contracts N01-NS-9-2314, -2315, -2316, -2317, -2319 and -2320). The views stated herein do not necessarily represent the official views of the National Institutes of Health (National Institute of Child Health and Human Development, National Institute on Drug Abuse, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke), or the Department of Health and Human Services, nor any other agency of the United States government.

Children and adolescents with critical cyanotic congenital heart disease (CHD) are at risk for deficits in aspects of executive function (EF). The primary aim of this investigation was to compare EF outcomes in three groups of children/adolescents with severe CHD and controls (ages 10–19 years). Participants included 463 children/adolescents with CHD [dextro-transposition of the great arteries (TGA), n=139; tetralogy of Fallot (TOF), n=68; and, single-ventricle anatomy requiring Fontan procedure (SVF), n=145] and 111 controls, who underwent laboratory and informant-based evaluation of EF skills. Rates of EF impairment on D-KEFS measures were nearly twice as high for CHD groups (75–81%) than controls (43%). Distinct EF profiles were documented between CHD groups on D-KEFS tasks. Deficits in flexibility/problem-solving and verbally mediated EF skills were documented in all three CHD groups; visuo-spatially mediated EF abilities were impaired in TOF and SVF groups, but preserved in TGA. Parent, teacher, and self-report ratings on the BRIEF highlighted unique patterns of metacognitive and self-regulatory concerns across informants. CHD poses a serious threat to EF development. Greater severity of CHD is associated with worse EF outcomes. With increased understanding of the cognitive and self-regulatory vulnerabilities experienced by children and adolescents with CHD, it may be possible to identify risks early and provide individualized supports to promote optimal neurodevelopment. (JINS, 2014, 20, 34–49)

Severe traumatic brain injury (TBI) leads to physical, neuropsychological, and emotional deficits that interfere with the individual's capacity to return to his or her former lifestyle. This review focuses on social cognition, that is, the capacity to attend to, recognize and interpret interpersonal cues that guide social behavior. Social cognition entails “hot” processes, that is, emotion perception and emotional empathy and “cold” processes, that is, the ability to infer the beliefs, feelings, and intentions of others (theory of mind: ToM) to see their point of view (cognitive empathy) and what they mean when communicating (pragmatic inference). This review critically examines research attesting to deficits in each of these domains and also examines evidence for theorized mechanisms including specific neural networks, the role of simulation, and non-social cognition. Current research is hampered by small, heterogeneous samples and the inherent complexity of TBI pathology. Nevertheless, there is evidence that facets of social cognition are impaired in this population. New assessment tools to measure social cognition following TBI are required that predict everyday social functioning. In addition, research into remediation needs to be guided by the growing empirical base for understanding social cognition that may yet reveal how deficits dissociate following TBI. (JINS, 2013, 19, 1–16)

Tulving’s (1972) theory of memory draws a distinction between general knowledge (semantic memory) and memory for events (episodic memory). Neuropsychological studies have generally examined each type of memory in isolation, but theorists have long argued that these two forms of memory are interdependent. Here we review several lines of neuropsychological research that have explored the interdependence of episodic and semantic memory. The studies show that these forms of memory can affect each other both at encoding and at retrieval. We suggest that theories of memory should be revised to account for all of the interdependencies between episodic and semantic memory; they should also incorporate forms of memory that do not fit neatly into either category. (JINS, 2010, 16, 748–753.)

Testing hypotheses derived from neuropsychological models of mood, as well as the association of mood states and personality characteristics with global-local visual processing, were examined. Fifty-nine men completed measures associated with depression and positive mood, and were administered a brief perceptual judgment task that assessed global-local visual processing biases. Additionally, 19 of these 59 subjects were administered measures of anxiety and optimism-pessimism and completed an expanded judgment task. Affective and personality variables were then correlated with judgment task performances. Consistent with predictions, positive mood and optimism were directly associated with a global bias and inversely related to a local bias. A converse pattern of findings was obtained with depression and trait anxiety. Implications for research concerning other aspects of visual processing are discussed. (JINS, 1996, 2, 249–255.)

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular. (JINS, 2006, 12, 707–735.)

Objectives: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. Methods: We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. Results: The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. Conclusions: TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. (JINS, 2016, 22, 120–137)

Because of its high prevalence and implications for quality of life and possibly even disease progression, depression has been intensively studied in multiple sclerosis (MS) over the past 25 years. Despite the publication of numerous excellent empirical research papers on this topic during that time, the publication of theoretical work that attempts to explain depression in a comprehensive way is scarce. In this study, we present a theoretical model that attempts to integrate existing work on depression in MS and provide testable hypotheses for future work. The model suggests that risk for depression begins with the onset of MS. MS results in disease-related changes such as increased lesion burden/brain atrophy and immunological anomalies that are associated with depression in MS, but explain only a relatively limited proportion of the variance. Common sequelae of MS including fatigue, physical disability, cognitive dysfunction, and pain, have all been shown to have an inconsistent or relatively weak relationship to depression in the literature. In the model, we propose that four variables—social support, coping, conceptions of the self and illness, and stress—may moderate the relationship between the above common MS sequelae with depression and help to explain inconsistencies in the literature. (JINS, 2008, 14, 691–724.)

The behavioral syndrome resulting from damage to the ventromedial prefrontal (VM) region presents major challenges for clinical assessment and management, stemming from the absence of reliable neurologic or psychometric markers, coupled with often debilitating impairments of decision-making and behavior regulation. Damage to this region disrupts neural circuitry critical for emotion, which in turn may contribute to impairments in real-world competencies. Here we present findings from patients with focal lesions in the VM region acquired either in childhood or adulthood, and show that there is a relationship between emotional dysfunction and impairments in real-world behavioral competencies. Emotion was rated by participants' relatives on dimensions including frustration tolerance, lability, anxiety, and blunted affect. Real-world competencies were rated by the relatives on dimensions including judgment, planning, and initiation, and were evaluated by clinician ratings in areas including social, financial, and occupational function. VM damage resulted in severe disruption of emotion, and this emotional dysfunction accounted for a significant portion of impaired real-world competencies. The long-term impairments associated with childhood-onset lesions were at least as severe as those resulting from adult-onset damage. Greater focus on the contribution of emotional dysfunction to the real-world competencies of patients with damage in the VM region may sharpen their neuropsychological assessment and facilitate rehabilitation efforts. (JINS, 2006, 12, 224–235.)